Hypothesizing that the intranasal administration of streptozotocin would be a valid model of Alzheimer’s disease-like dementia

Abstract

Streptozotocin (STZ) is a glucose analogue containing an N-methyl-N-nitrosurea group that is used to induce experimental diabetes mellitus in rodents and clinically as a chemotherapeutic for neuroendocrine tumors. As it does not cross the blood brain barrier, STZ is also administered intracerebroventricularly to induce a widely-used Alzheimer’s disease (AD)-like pre-clinical model of dementia. In this work, we aim to briefly discuss some structural and functional aspects of the intranasal barrier, raising the hypothesis that STZ could be used to induce a dementia model via its nasal instillation. We approached intranasal administration as a possible route to reach the hippocampus, independently of the presence of the GLUT-2 glucose transporter in olfactory cells, which is capable of transporting STZ. We then discuss the neurotoxicity of STZ to neural cells and finally propose how this hypothesis could be confirmed experimentally. This alternative AD-like model of dementia would be very attractive for preclinical studies, as it is less invasive, simpler (since it does not require a surgical procedure), cheaper and less stressful for animals.